The basic aim of the proposed research is to use experimental teratocarcinoma in mammals as the model for studies of processes controlling normal differentiation and neoplasia. Transfer of early mammalian embryos and/or genital ridges to various extra-uterine sites results in the appearance of teratoma (benign tumors composed of mature somatic tissues) or teratocarcinoma (malignant tumors which in addition possess embryonal carcinoma cells). Embryonal carcinoma cells (ECC) are pluripotent stem cells of teratocarcinoma able to proliferate as undifferentiated cells but can also differentiate into various somatic tissues. Factors which regulate the destiny of a grafted embryo i.e., whether it will become teratoma or teratocarcinoma, are probably multiple and so far barely investigated. We are planning to explore in detail both embryo- and host-related factors which direct the differentiation of transplanted embryos. In animals bearing teratoma and/or teratocarcinoma long-range changes like splenomegaly, hepatomegaly, extramedullary hematopoiesis, and changes in immune response to teratocarcinoma cells also will be investigated. Pattern and control of differentiation (histogenesis) of ECC in vivo and in vitro will be followed using tissue specific histochemical and biochemical markers. Cell hybridization of ECC with differentiated somatic cells and subsequent testing of hybrids for tumorigenesis and ability to differentiate would give insight into the control of the differentiated state and malignancy.